The main objective of this project is to investigate the ecology and epidemiology of newly recognized protozoal Babesia spp. in California. Preliminary studies suggest that the transmission dynamics of this emerging zoonosis may differ from that of Babesia microti the cause of human babesiosis in the eastern and midwestern parts of the United States. Molecular analysis of Babesia in blood samples from 4 recent clinical cases of babesiosis in California showed that the parasites were genotypically distinct from B. microti and phylogenetically more closely related to WA1, a newly recognized Babesia that was isolated from a patient in Washington. Serologic analysis suggests that the babesial parasites infecting humans in California are antigenically similar to species that we have isolated from Black-tailed Deer (Odocoileus hemionus) and Bighorn Sheep (Ovis canadensis). The primary hypothesis being tested is that wild mammals, most notably rodents and deer, serve as reservoirs for babesial parasites that are transmitted to humans in California. In the first phase of the study, a servosurvey of humans, rodents and deer in areas where human cases of babesiosis have occurred and in control areas will be performed to assess the seroprevalence of the Babesia species. Babesial isolates obtained from humans and wildlife will be antigenically and genotypically compared. Molecular characterization will involve southern blot analysis using Babesia specific probes and analysis of the nuclear small subunit RNA gene sequences amplified by the polymerase chain reaction (PCR). Ticks collected in these areas will be screened for Babesia by PCR amplification of parasite sequences using isolate specific primers. In the second phase, risk factors associated with acquiring Babesia will be evaluated in a retrospective case-control study and investigated via mathematical models. Vector competence of Ixodes pacificus the purported vector, will be evaluated via tick transmission studies in deer. The utilization of molecular detection methods in this epidemiologic study allows for better detection and characterization of the babesial parasite in chronically infected humans and potential wildlife reservoirs.